Development of anti-membrane type 1-matrix metalloproteinase nanobodies as immunoPET probes for triple negative breast cancer imaging.

Mulero, FranciscaOteo, MartaGaraulet, GuillermoMagro, NataliaRebollo, LluviaMedrano, GuillermoCampos Olivas, RamonSantiveri, ClaraSellek, Ricela EMargolles, YagoArroyo, Alicia GFernández, Luis AngelMorcillo, Miguel AngelMartinez Torrecuadrada, Jorge Luis2023-06-012023-06-012022-11-24Front Med (Lausanne). 2022 ;9:1058455.2296-858Xhttp://hdl.handle.net/20.500.12105/16133Triple-negative breast cancer (TNBC) is characterized by aggressiveness and high rates of metastasis. The identification of relevant biomarkers is crucial to improve outcomes for TNBC patients. Membrane type 1-matrix metalloproteinase (MT1-MMP) could be a good candidate because its expression has been reported to correlate with tumor malignancy, progression and metastasis. Moreover, single-domain variable regions (VHHs or Nanobodies) derived from camelid heavy-chain-only antibodies have demonstrated improvements in tissue penetration and blood clearance, important characteristics for cancer imaging. Here, we have developed a nanobody-based PET imaging strategy for TNBC detection that targets MT1-MMP. A llama-derived library was screened against the catalytic domain of MT1-MMP and a panel of specific nanobodies were identified. After a deep characterization, two nanobodies were selected to be labeled with gallium-68 (68Ga). ImmunoPET imaging with both ([68Ga]Ga-NOTA-3TPA14 and [68Ga]Ga-NOTA-3CMP75) in a TNBC mouse model showed precise tumor-targeting capacity in vivo with high signal-to-background ratios. (68Ga)Ga-NOTA-3CMP75 exhibited higher tumor uptake compared to (68Ga)Ga-NOTA-3TPA14. Furthermore, imaging data correlated perfectly with the immunohistochemistry staining results. In conclusion, we found a promising candidate for nanobody-based PET imaging to be further investigated as a diagnostic tool in TNBC.engSMURhttp://creativecommons.org/licenses/by-nc-sa/4.0/immunoPETMT1-MMPNANOBODIESGALIUM-68TNBC (Triple negative breast cancer)Development of anti-membrane type 1-matrix metalloproteinase nanobodies as immunoPET probes for triple negative breast cancer imaging.Atribución-NoComercial-CompartirIgual 4.0 Internacional365075409105845510.3389/fmed.2022.1058455Frontiers in medicineopen access